The overall objective of this project is to explore in detail the processes involved in the expression of tissue specific functions by liver cells. The results will be interpreted to further understand normal liver development and function, and to elucidate changes resulting from hepatocarcinoma. The cell line Hepa, derived from the mouse hepatoma BW 7756 (Jackson Laboratory) secretes three serum proteins into the culture medium. Two of these have been identified as albumin and alpha- fetoprotein. The third has tentatively been identified as transferrin. The cellular rates of synthesis of these proteins are dependent upon the phase and duration of the cell cycle. The synthesis of albumin has been studied in the most detail. The rates of albumin synthesis by Hepa under various growth conditions completely span synthetic rates measured in equivalent amounts of liver tissue. In synchronous cultures, the rate of albumin synthesis increases during mitosis indicating that the albumin mRNA may be associated with and stabilized by the nuclear membrane. Two basic parameters govern the cellular rate of protein synthesis: 1) the translation rate and 2) the cellular number of translation sites. These two parameters will be evaluated for albumin, alpha-fetoprotein, and "transferrin" synthesis under various growth conditions and in synchronous cells. The possible role of the nuclear membrane in mRNA stabilization will be further investigated in Hepa and compared with normal mouse liver.